Pegcetacoplan Could Halt Disease Progression in C3 Glomerulopathy, IC-MPGN, with Daniel Gale, PhD, MB BChir

A new analysis from the phase 3 VALIANT trial reinforces the potential of pegcetacoplan (Empaveli) as a disease-modifying therapy for C3 glomerulopathy (C3G) and idiopathic immune-complex membranoproliferative glomerulonephritis (IC-MPGN).

Results of the study, which were presented at the 62nd European Renal Association (ERA 2025) Congress, suggest use of pegcetacoplan was associated with improvements in complement biomarkers, sustained reductions in proteinuria, and early signs of kidney protection.

“It’s an exciting trial to see those data and the 3 things that they showed was the striking 60% reduction in proteinuria, the really clear evidence of stabilization of GFR compared with a placebo arm that lost 7.5 mLs per minute in just 6 months, and, perhaps most strikingly, was the biopsy appearances, where 70% of the patients there was no C3 deposited on the biopsy after 6 months when it was present,” explained Daniel Gale, MBChB, PhD, director of the UK-based RaDaR Registry and the St Peter's Chair of Nephrology at University College London, in an interview.

In the 124-patient trial, participants received subcutaneous pegcetacoplan or placebo twice weekly for 26 weeks in addition to background therapy. The original results were presented at the American Society of Nephrology’s Kidney Week 2024 and demonstrated pegcetacoplan was associated with a statistically significant and clinically meaningful 68% (P <.0001) reduction in proteinuria compared to placebo at week 26.1,2

In the ERA 2025 study presented by Gale, the pegcetacoplan group showed robust complement rebalancing by week 4, with serum C3 rising by 308.7 mg/dL (SD, 94.7) and soluble C5b-9 decreasing by 612.3 ng/mL (SD, 614.7). Of note, no biomarker improvements were observed in the placebo group.1

At week 26, 71% of pegcetacoplan-treated patients had complete clearance of glomerular C3c on biopsy. In terms of proteinuria, pegcetacoplan showed rapid and sustained effect: by week 4, reductions were apparent, and by week 26, 50.8% of patients (32/63) had UPCR less than 1 g/g, including 31.7% below 0.5 g/g. In contrast, the placebo arm showed no meaningful shift across proteinuria strata, with patients remaining in higher UPCR ranges or worsening.1

In the study presented by Gale, investigators noted previous registry data show patients who achieve UPCR less than 0.88 g/g within the first year of diagnosis have an 87% reduction in long-term risk of kidney failure. In VALIANT, half of pegcetacoplan-treated patients reached this threshold by week 26.1

To learn more about how pegcetacoplan could shift the treatment paradigm in C3G and IC-MPGN, watch our full interview with Dr Gale from ERA 2025.

Relevant disclosures for Gale include Novartis, Alexion, Calliditas, Britannia, Vifor, Judo Bio, Adnovate, Sanofi, Anlylam, Boehringer Ingelheim, and Bayer.

References:

1. Gale DP, Bomback AS, Licht C, et al. Pegcetacoplan Treatment Appears to Halt Disease Progression in C3G and Primary (Idiopathic) IC-MPGN Patients: Results from the Phase 3 VALIANT Study. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

2. Campbell P. VALIANT: Pegcetacoplan Offers Benefit for UPCR, eGFR, C3 Staining in C3G, IC-MPGN. HCP Live. Published October 26, 2024. Accessed June 8, 2025. https://www.hcplive.com/view/valiant-pegcetacoplan-offers-benefit-for-upcr-egfr-c3-staining-in-c3g-ic-mpgn